增加的SARS-CoV-2 IgG4具有可变的后果,取决于Fc功能,Fc受体多态性和病毒变异
L Carissa Aurelia1, Ruth A Purcell1, Robert M Theisen2
1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.
Science advances
|February 26, 2025
概括
重复接种COVID-19疫苗可以提高免疫球蛋白G4 (IgG4) 的水平. 升高的IgG4可以损害某些免疫反应,但可能会增强其他免疫反应,这取决于总抗体水平和病毒变异.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 分子生物学分子生物学
背景情况:
- 重复的mRNACOVID-19疫苗接种与高峰特异性免疫球蛋白G4 (IgG4) 标位的增加有关.
- 升高IgG4对Fc介导免疫反应的功能后果仍然不完全理解.
研究的目的:
- 描述高峰特异性IgG4标位增加对各种Fc介导免疫功能的影响.
- 研究IgG4,其他IgG子类和Fc受体 (FcγR) 相互作用之间的相互作用.
- 探索SARS-CoV-2变种对这些Fc介导反应的影响.
主要方法:
- 疫苗接种后不同IgG4标位的个体中Fc介导反应的表征.
- 评估FcγR结合,抗体依赖性细胞毒性 (ADCC) 和抗体依赖性细胞化 (ADCP).
- 在模型中,结合了抗体子类度和FcγR多态.
主要成果:
- 增高的尖端特异性IgG4降低了FcγRIIIa结合和抗体依赖性细胞毒性 (ADCC).
- 在具有较低总尖峰特异性IgG的个体中,IgG4增强了FcγRI和FcγRIIa结合和抗体依赖细胞化 (ADCP).
- 这种协同效应在最近的SARS-CoV-2变种中更加明显,导致较低的总尖峰特异标位.
结论:
- 提高IgG4对Fc功能的影响取决于情境,受总IgG水平和抗原因素的影响.
- 在Fc介导免疫中IgG4的作用是复杂的,在特定条件下可能增强细胞分裂.
- 这些发现强调了在评估疫苗诱导的免疫反应时需要考虑抗体子类动态和抗原变异性的必要性.
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